We have begun studies to interrupt primary oncogenesis using the tetrapeptide, tuftsin. The immunological adjuvant was administered to newborns which received Rous chicken tumor cells (RCTC). Tuftsin has been shown to stimulate the cytotoxicity of several effector cell populations. We will monitor the effect of this compound on the development of primary tumors. Preliminary experiments suggested that cell(s) which enhanced tumor formation in these mice was not a conventional T cell, B cell or adherent macrophage. These data were obtained by depleting the spleen cells of T or B cells using specific antibody and complement, and removing macrophages by adherence to plastic. In recent studies we have repeated these experiments using a multiple step adherence protocol where spleen cells were allowed to adhere to plastic three separate times. The nonadherent cells were greater than 98% macrophage free as determined by nonspecific esterase staining. In another series of experiments RCTC-infected newborns receive spleen or lymph node cells from V+T- mice on day one. Although a decrease in tumor incidence was observed in this group, the tumor incidence in the control group was so low that statistical significance could not be demonstrated. The identification of the cell types responsible for the increased tumor incidence in B10.D2 mice has not been determined. Elimination studies performed to date using specific antiserum and complement indicated that B cells and probably Thy 1.2-bearing cells are not responsible for the increase in tumor incidence. Further studies are necessary to identify the cell type(s) responsible for these observations. Studies were performed in an attempt to interrupt primary oncogenesis by stimulating macrophages and NK cells using the tetrapeptide, tuftsin. B10 mice were given RCTC as newborns and then various doses of tuftsin. The significance of the data indicates the importance of the immune response in primary tumorigenesis. Under the appropriate conditions, the immune response can enhance the appearance of primary tumors. Normal adult mice possess a non-T, non-B, adherent cell which greatly enhances tumor development if present after the primary oncogenic event has occurred. The development of primary tumors can be reduced by use of tuftsin. Further, identification of the cells and the mechanisms by which they expect their effects could contribute to the design of further immunotherapy protocols.